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1.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde | ID: lis-48012

RESUMO

Pacientes com hanseníase resistentes a medicamentos já ofertados na rede pública passam a contar com um novo tratamento disponível no Sistema Único de Saúde (SUS). O antibiótico Claritromicina já é utilizado no SUS para o tratamento de outras patologias, como infecções de vias aéreas superiores e inferiores, infecções na pele e tecidos moles, entre outros, e agora passa a fazer parte do rol de medicamentos para tratamento da hanseníase.


Assuntos
Hanseníase/tratamento farmacológico , Claritromicina/farmacologia , Sistema Único de Saúde
2.
Food Chem ; 343: 128410, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33406573

RESUMO

Monascus, which is traditionally used in various Asian industries, produces several secondary metabolites during the fermentation process, including citrinin, a toxin whose impact limits the development of the Monascus industry. We have previously found that the addition of 2.0 g/L genistein to Monascus medium reduces citrinin production by approximately 80%. Here, we explored the molecular mechanisms whereby genistein affects citrinin production. We sequenced the Monascus genome and performed transcriptome analysis on genistein-treated and -untreated groups. Comparison between the two groups showed 378 downregulated and 564 upregulated genes. Among the latter, we further examined the genes related to citrinin biosynthesis and quantified them using quantitative real-time polymerase chain reaction (qRT-PCR). Genes orf5, pksCT, orf3, orf1, orf6, and ctnE were significantly downregulated, demonstrating that genistein addition indeed affects citrinin synthesis. Our results may lay the groundwork for substantial improvements in the Monascus fermentation industry.


Assuntos
Citrinina/biossíntese , Genisteína/farmacologia , Monascus/química , Transcriptoma/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Ontologia Genética , Genes Fúngicos , Monascus/genética , Monascus/metabolismo , Família Multigênica , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima/efeitos dos fármacos
3.
Food Chem ; 343: 128417, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33406574

RESUMO

This study aimed to investigate the structural and antimicrobial properties of Maillard reaction products (MRPs) in chicken liver protein (CLP) and its hydrolysate (CLPH) after sonication (SCLPH). The MRPs of CLP (CLPM), CLPH (CLPHM) and SCLPH (SCLPHM) were analyzed by several spectrometric techniques. The molecular weights of the CLPHM and SCLPHM were primarily between 1.35 kDa and 17 kDa. Moreover, the molecular weights in the CLPHM and SCLPHM below 1.35 kDa were increased, which indicated that cross-linking and thermal degradation occurred during the Maillard reaction (MR). The SCLPHM showed an obvious network skeleton, and the surface had many small crystal-shaped particles after ultrasound treatment and MR by scanning electron microscopy. The SCLPHM had more negative charges than the CLPHM, thus effectively inhibiting the growth of S. saprophyticus and E. coli. MR and ultrasound treatment could be a promising technology to expand the application prospects of low-value meat byproducts.


Assuntos
Antibacterianos/química , Fígado/metabolismo , Hidrolisados de Proteína/química , Animais , Antibacterianos/farmacologia , Galinhas , Escherichia coli/efeitos dos fármacos , Reação de Maillard , Peso Molecular , Hidrolisados de Proteína/farmacologia , Sonicação , Staphylococcus saprophyticus/efeitos dos fármacos , Temperatura de Transição
4.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(1): 104-110, 2021 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-33448207

RESUMO

Objective: After using hyaluronic acid (HA) to modify curcumin (CUR), the effects of calcium phosphate cement (CPC) combined with HA/CUR on the proliferation and osteogenesis of osteoblasts were investigated. Methods: First, HA and CUR were esterified and covalently combined to prepare HA/CUR, and the characteristics were observed and the infrared spectrum was tested. Then, HA, CUR, and HA/CUR were mixed with CPC according to 5% ( W/ W) to prepare HA-CPC, CUR-CPC, and HA/CUR-CPC, respectively. Setting time detection, scanning electron microscope observation, injectable performance test, and compression strength test were conducted; and the CPC was used as a control. Osteoblasts were isolated and cultured from the skull of newborn Sprague Dawley rats, and the 2nd generation cells were cultured with the 4 types of bone cement, respectively. The effects of HA/CUR-CPC on the proliferation and osteogenesis of osteoblasts were estimated by the scanning electron microscopy observation, live/dead cell fluorescence staining, cell counting, osteopontin (OPN) immunofluorescence staining, alkaline phosphatase (ALP) staining,and alizarin red staining. Results: Infrared spectroscopy test showed that HA and CUR successfully covalently combined. The HA/CUR-CPC group had no significant difference in initial setting time, final setting time, injectable rate, and compressive strength when compared with the other 3 groups ( P>0.05); scanning electron microscope observation showed that HA/CUR was scattered on CPC surface. After co-culture of bone cement and osteoblasts, scanning electron microscopy observation showed that the osteoblasts, which had normal morphology and the growth characteristics of osteoblasts, clustered and adhered to HA/CUR-CPC. There was no significant difference in cell survival rate between HA/CUR-CPC group and other groups ( P>0.05), and the number of cells significantly increased ( P<0.05); the degrees of OPN immunofluorescence staining, ALP staining, and alizarin red staining were stronger than other groups. Conclusion: HA/CUR-CPC has good biocompatibility and mechanical properties, which can promote the proliferation and osteogenesis of osteoblasts.


Assuntos
Curcumina , Osteogênese , Animais , Cimentos para Ossos , Fosfatos de Cálcio/farmacologia , Proliferação de Células , Curcumina/farmacologia , Ácido Hialurônico/farmacologia , Osteoblastos , Ratos , Ratos Sprague-Dawley
6.
Pest Manag Sci ; 77(1): 313-324, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33411414

RESUMO

BACKGROUND: The investigation of molecular mechanisms and evolution of resistance to insecticides is an ongoing challenge, as researchers must provide guidance to manage the resistance to achieve sustainable production in agriculture. Predicting, monitoring, and managing insecticide resistance requires information on the origins, selection, and spread of resistance genes. The resistance of Plutella xylostella (L.) against diamide insecticides is becoming an increasingly severe problem in east and southeast Asia. In this study, the evolution of resistance was investigated using a resistance allele [ryanodine receptor (RyR); G4946E mutation] and its flanking regions, as well as mitochondrial cytochrome c oxidase subunit I (mtCOI). RESULTS: The sequences of the flanking region of the G4946E and mtCOI suggested that the G4946E mutation has a key role in resistance. Furthermore, the G4946E mutation has multiple origins, and congenic resistant mutations have spread across east and southeast Asia, despite substantial geographical barriers. In addition, the susceptibility of field populations partially recovered during winter, based on the observed decrease in the G4946E (resistant allele) frequency. Finally, the resistance level indexed by the frequency of the E4946 allele was significantly lower in non-overwintering regions than in overwintering regions. CONCLUSION: The information of the present study is useful to monitor resistance using molecular markers and to develop strategies to delay the evolution of diamide resistance.


Assuntos
Inseticidas , Mariposas , Alelos , Animais , Ásia Sudeste , Diamida , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Mariposas/genética
7.
PLoS Negl Trop Dis ; 15(1): e0008895, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395417

RESUMO

A wide variety of symptoms is associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and these symptoms can overlap with other conditions and diseases. Knowing the distribution of symptoms across diseases and individuals can support clinical actions on timelines shorter than those for drug and vaccine development. Here, we focus on zinc deficiency symptoms, symptom overlap with other conditions, as well as zinc effects on immune health and mechanistic zinc deficiency risk groups. There are well-studied beneficial effects of zinc on the immune system including a decreased susceptibility to and improved clinical outcomes for infectious pathogens including multiple viruses. Zinc is also an anti-inflammatory and anti-oxidative stress agent, relevant to some severe Coronavirus Disease 2019 (COVID-19) symptoms. Unfortunately, zinc deficiency is common worldwide and not exclusive to the developing world. Lifestyle choices and preexisting conditions alone can result in zinc deficiency, and we compile zinc risk groups based on a review of the literature. It is also important to distinguish chronic zinc deficiency from deficiency acquired upon viral infection and immune response and their different supplementation strategies. Zinc is being considered as prophylactic or adjunct therapy for COVID-19, with 12 clinical trials underway, highlighting the relevance of this trace element for global pandemics. Using the example of zinc, we show that there is a critical need for a deeper understanding of essential trace elements in human health, and the resulting deficiency symptoms and their overlap with other conditions. This knowledge will directly support human immune health for decreasing susceptibility, shortening illness duration, and preventing progression to severe cases in the current and future pandemics.


Assuntos
/tratamento farmacológico , Zinco/administração & dosagem , Zinco/deficiência , Anti-Inflamatórios/farmacologia , /virologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Pandemias , Fatores de Risco , /isolamento & purificação
8.
Ecotoxicol Environ Saf ; 208: 111752, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396077

RESUMO

Arsenic is a toxic heavy metal vastly dispersed all over the earth crust. It manifests several major adverse health issues to millions of arsenic exposed populations. Arsenic is associated with different types of cancer, cardiovascular disorders, diabetes, hypertension and many other diseases. On the contrary, arsenic (arsenic trioxide, As2O3) is used as a chemotherapeutic agent in the treatment of acute promyelocytic leukemia. Balance between arsenic induced cellular proliferations and apoptosis finally decide the outcome of its transformation rate. Arsenic propagates signals via cellular and nuclear pathways depending upon the chemical nature, and metabolic-fates of the arsenical compounds. Arsenic toxicity is propagated via ROS induced stress to DNA-repair mechanism and mitochondrial stability in the cell. ROS induced alteration in p53 regulation and some mitogen/ oncogenic functions determine the transformation outcome influencing cyclin-cdk complexes. Growth factor regulator proteins such as c-Jun, c-fos and c-myc are influenced by chronic arsenic exposure. In this review we have delineated arsenic induced ROS regulations of epidermal growth factor receptor (EGFR), NF-ĸß, MAP kinase, matrix-metalloproteinases (MMPs). The role of these signaling molecules has been discussed in relation to cellular apoptosis, cellular proliferation and neoplastic transformation. The arsenic stimulated pathways which help in proliferation and neoplastic transformation ultimately resulted in cancer manifestation whereas apoptotic pathways inhibited carcinogenesis. Therapeutic strategies against arsenic should be designed taking into account all these factors.


Assuntos
Arsênico/fisiologia , Proliferação de Células/fisiologia , Plásticos/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Arsênico/metabolismo , Trióxido de Arsênio/metabolismo , Trióxido de Arsênio/farmacologia , Arsenicais/metabolismo , Proliferação de Células/efeitos dos fármacos , Humanos , Mitocôndrias/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neoplasias , Óxidos/toxicidade , Transdução de Sinais/efeitos dos fármacos
9.
Ecotoxicol Environ Saf ; 208: 111758, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396081

RESUMO

The cultivation of leafy vegetables on metal contaminated soil embodies a serious threat to yield and quality. In the present study, the potential role of exogenous jasmonic acid (JA; 0, 5, 10, and 20 µM) on mitigating chromium toxicity (Cr; 0, 150, and 300 µM) was investigated in choysum (Brassica parachinensis L.). With exposure to increasing Cr stress levels, a dose-dependent decline in growth, photosynthesis, and physio-biochemical attributes of choysum plants was observed. An increase in Cr levels also resulted in oxidative stress closely associated with higher lipoxygenase activity (LOX), hydrogen peroxide (H2O2) generation, lipid peroxidation (MDA), and methylglyoxal (MG) levels. Exogenous application of JA alleviated the Cr-induced phytotoxic effects on photosynthetic pigments, gas exchange parameters, and restored growth of choysum plants. While exposed to Cr stress, JA supplementation induced plant defense system via enhanced regulation of antioxidant enzymes, ascorbate and glutathione pool, and the glyoxalase system enzymes. The coordinated regulation of antioxidant and glyoxalase systems expressively suppressed the oxidative and carbonyl stress at both Cr stress levels. More importantly, JA restored the mineral nutrient contents, restricted Cr uptake, and accumulation in roots and shoots of choysum plants when compared to the only Cr-stressed plants. Overall, the application of JA2 treatment (10 µM JA) was more effective and counteracted the detrimental effects of 150 µM Cr stress by restoring the growth and physio-biochemical attributes to the level of control plants, while partially mitigated the detrimental effects of 300 µM Cr stress. Hence, JA application might be considered as an effective approach for minimizing Cr uptake and its detrimental effects in choysum plants grown on contaminated soils.


Assuntos
Antioxidantes/farmacologia , Brassica/fisiologia , Cromo/toxicidade , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Poluentes do Solo/toxicidade , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Brassica/efeitos dos fármacos , Brassica/metabolismo , Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Oxirredução , Estresse Oxidativo/fisiologia , Fotossíntese/efeitos dos fármacos , Folhas de Planta/metabolismo
10.
Ecotoxicol Environ Saf ; 208: 111579, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396102

RESUMO

Studies about radiation damage in vivo are very significant for healthy risk assessment as well as cancer radiotherapy. Ceramide as a second messenger has been found to be related to radiation-induced apoptosis. However, the detailed mechanisms in living systems are still not fully understood. In the present study, the effects of ceramide in gamma radiation-induced response were investigated using Caenorhabditis elegans. Our results indicated that ceramide was required for gamma radiation-induced whole-body germ cell apoptosis by the production of radical oxygen species and decrease of mitochondrial transmembrane potential. Using genetic ceramide synthase-related mutated strains and exogenous C16-ceramide, we illustrated that ceramide could regulate DNA damage response (DDR) pathway to mediate radiation-induced germ cell apoptosis. Moreover, ceramide was found to function epistatic to pmk-1 and mpk-1 in MAPK pathway to promote radiation-induced apoptosis in Caenorhabditis elegans. These results demonstrated ceramide could potentially mediated gamma radiation-induced apoptosis through regulating mitochondrial function, DDR pathway and MAPK pathway.


Assuntos
Caenorhabditis elegans/fisiologia , Ceramidas/farmacologia , Protetores contra Radiação/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos da radiação , Proteínas de Caenorhabditis elegans/genética , Ceramidas/metabolismo , Dano ao DNA , Células Germinativas/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Radiação , Espécies Reativas de Oxigênio/metabolismo
11.
Nat Commun ; 12(1): 26, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397915

RESUMO

Mitochondrial oxidation-induced cell death, a physiological process triggered by various cancer therapeutics to induce oxidative stress on tumours, has been challenging to investigate owing to the difficulties in generating mitochondria-specific oxidative stress and monitoring mitochondrial responses simultaneously. Accordingly, to the best of our knowledge, the relationship between mitochondrial protein oxidation via oxidative stress and the subsequent cell death-related biological phenomena has not been defined. Here, we developed a multifunctional iridium(III) photosensitiser, Ir-OA, capable of inducing substantial mitochondrial oxidative stress and monitoring the corresponding change in viscosity, polarity, and morphology. Photoactivation of Ir-OA triggers chemical modifications in mitochondrial protein-crosslinking and oxidation (i.e., oxidative phosphorylation complexes and channel and translocase proteins), leading to microenvironment changes, such as increased microviscosity and depolarisation. These changes are strongly related to cell death by inducing mitochondrial swelling with excessive fission and fusion. We suggest a potential mechanism from mitochondrial oxidative stress to cell death based on proteomic analyses and phenomenological observations.


Assuntos
Irídio/farmacologia , Mitocôndrias/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Morte Celular/efeitos dos fármacos , Reagentes para Ligações Cruzadas/química , Transferência de Energia , Células HEK293 , Células HeLa , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Oxirredução/efeitos dos fármacos , Proteoma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Viscosidade
12.
Blood Coagul Fibrinolysis ; 32(1): 44-49, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33417336

RESUMO

There is an increasing evidence supporting the existence of coagulopathy in coronavirus disease 2019 (COVID-19) patients. Most of reports are mainly focused on d-dimer. Our objective is to describe coagulation parameters in these patients that could be involved in a hypercoagulate state and to test platelet function to see if there are short closure times. We analyzed coagulation samples from 80 patients admitted with COVID-19 in our hospital. We also tested platelet function by closure times in a small subgroup of patients. Most of samples had increased d-dimer (96.2%) (median of d-dimer: 1158 ng/ml FEU), increased fibrinogen (75.2%) (median: 5.23 g/l), increased factor VIII (86%) (median: 264.8 U/dl), decreased protein S (22.5% of women, 62.5% of men) (median: 62.8 and 68.5 U/dl, respectively), decreased protein C (7.6%) (median: 100 U/dl), decreased factor XII (25.3%) (median: 90.3 U/dl) and decreased antithrombin activity (21%) (median: 86 U/dl). International normalized ratio was higher than normal in 24 patients (30%) (median: 1.13). The activated partial thromboplastin time ratio was below the normal range in nine patients (11.2%) and above normal in three (3.75%) (median: 0.93). The closure times were short in the 20% and 40% of samples of collagen and ADP and collagen and epinephrine, respectively. Twelve of the 80 patients (15%) had a thrombotic event and all had several abnormal coagulation parameters related with increased thrombotic risk. The results of this study support a hypercoagulability state in COVID-19 patients and it may help to explain the microvascular thrombosis caused by the inflammatory response.


Assuntos
Anticoagulantes/uso terapêutico , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/etiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/efeitos adversos , Testes de Função Plaquetária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias
13.
Ecotoxicol Environ Saf ; 208: 111724, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396055

RESUMO

In recent years, in order to promote animal growth and reduce the risk of disease, a variety of antibiotics are frequently added to the animal feed of livestock and poultry. However, these antibiotics can not be fully digested by animals and most of them are excreted with feces, consequently causing the enrichment of antibiotic resistance genes (ARGs) and huge environmental risks. Nowadays, composting is a better option to solve these problems. Accordingly, this study explored the effects of co-composting swine manure with different inoculants dominated by Phanerochaete chrysosporium (p), Aspergillus niger (a), and Bacillus licheniformis (b) on the simultaneous removal of multiple antibiotics and resistance genes and evolution of the bacterial community. The results showed that the highest removal extent of tetracycline and oxytetracycline occurred in pile D (p:b:a=1:5:5, biomass) reaching 89.2% and 87.8%, respectively, while the highest removal extent of doxycycline and enrofloxacin occurred in pile A (p:b:a=1:0:0, biomass) reaching 98.6% and 89%, respectively. Compared with the levels in pile B (control check), in pile D, ARGs, except those for sulfonamides, decreased by 1.059 × 10-3-6.68 × 10-2 gene copies/16S rRNA copies. Inoculation with p alone effectively reduced intI1 and intI2. Canonical correspondence analysis (CCA) that microbial community structure evolution had a greater influence on ARGs than environmental factors. In summary, this study provided a feasible way to efficiently remove the antibiotics and antibiotic resistance genes in pig manure.


Assuntos
Antibacterianos/análise , Resistência Microbiana a Medicamentos/genética , Esterco/microbiologia , Ração Animal/análise , Animais , Antibacterianos/metabolismo , Bactérias/efeitos dos fármacos , Compostagem/métodos , Genes Bacterianos , Gado , Microbiota/efeitos dos fármacos , Oxitetraciclina/farmacologia , RNA Ribossômico 16S , Suínos , Tetraciclina/farmacologia
14.
Ecotoxicol Environ Saf ; 208: 111725, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396056

RESUMO

Aflatoxin B1 (AFB1) is a potent hepatotoxic and carcinogenic agent. Curcumin possesses potential anti-inflammatory, anti-oxidative and hepatoprotective effects. However, the role of LncRNAs in the protective mechanisms of curcumin against AFB1-induced liver damage is still elusive. Experimental broilers were randomly divided into 1) control group, 2) AFB1 group (1 mg/kg feed), 3) cur + AFB1 group (1 mg/kg AFB1 plus 300 mg/kg curcumin diet) and 4) curcumin group (300 mg/kg curcumin diet). Liver transcriptome analyses and qPCR were performed to identify shifts in genes expression. In addition, histopathological assessment and oxidant status were determined. Dietary AFB1 caused hepatic morphological injury, significantly increased the production of ROS, decreased liver antioxidant enzymes activities and induced inflammation and apoptosis. However, dietary curcumin partially attenuated the abnormal morphological changes, oxidative stress, and apoptosis in liver tissues. Transcriptional profiling results showed that 34 LncRNAs and 717 mRNAs were differentially expressed with AFB1 and curcumin co-treatment in livers of broilers. Analysis of the LncRNA-mRNA network, GO and KEGG enrichment data suggested that oxidative stress, inflammation and apoptosis pathway were crucial in curcumin's alleviating AFB1-induced liver damage. In conclusion, curcumin prevented AFB1-induced oxidative stress, inflammation and apoptosis through LncRNAs. These results provide new insights for unveiling the protective mechanisms of curcumin against AFB1-induced liver damage.


Assuntos
Aflatoxina B1/toxicidade , Curcumina/farmacologia , Fígado/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Galinhas/metabolismo , Dieta , Inflamação/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/farmacologia
15.
Ecotoxicol Environ Saf ; 208: 111739, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396067

RESUMO

Ultraviolet-B is an important fraction of sunlight which influences the plant performance either positively or adversely in terms of growth, physiology, biochemistry, and major active compounds. The static nature of plants constrains them to be subjected to various adverse environmental conditions. Several studies performed with plants and UV-B with fewer reports are available on medicinal plants having rhizome. The present study focuses on transformation induced in two Curcuma spp. (C. caesia and C. longa) under the influence of elevated UV-B (eUV-B) (ambient ±9.6 kJ m-2 d-1) under natural field conditions to analyse the changes in physiological, biochemical and essential oil of the test plants. eUV-B significantly reduced the photosynthetic activities such as photosynthetic rate (Ps), stomatal conductance (gs), transpiration (Tr), internal CO2 (Ci), and photochemical efficiency (Fv/Fm) with higher reductions in C. longa as compared to C. caesia. The enzymatic activities of PAL, CHI, and CAD showed higher stimulation in C. caesia whereas C. longa showed increment only in CAD. The essential oil content was increased by 16% and 9% in C. caesia and C. longa, respectively. C. caesia showed increased monoterpenes than sesquiterpenes, whereas almost equal increase of both the terpenoid found in C. longa. C. caesia showed induction of aromatic compounds (epiglobulol, germacrene, 4-terpineol), whereas anticancerous compounds; aphla-terpinolene (61%), beta-caryophyllene (60%), and beta-sesquiphellandrene (32%) were increased in C. longa. C. caesia acted well in terms of both physiology and major active compound (1, 8-cineole), but overall most of the compounds increased in C. longa under eUV-B.


Assuntos
Curcuma/efeitos da radiação , Raios Ultravioleta , Curcuma/química , Curcuma/fisiologia , Óleos Voláteis/farmacologia , Fotossíntese/efeitos dos fármacos , Extratos Vegetais , Plantas/efeitos dos fármacos , Rizoma/química , Terpenos
16.
Ecotoxicol Environ Saf ; 208: 111743, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396069

RESUMO

Autophagy dysregulation plays a pivotal role in cadmium (Cd)-induced nephrotoxicity. Quercetin (Qu), a flavonoid antioxidant with autophagy-enhancing effect, has protective effect on Cd-induced toxicity, but whether it can prevent Cd-induced nephrotoxicity via restoration of autophagy remains unknown. Here, primary rat proximal tubular (rPT) cells were exposed to Cd and/or Qu in vitro to clarify this issue. Data first showed that Cd-impaired autophagic flux was markedly alleviated by Qu, including decreased levels of autophagy marker proteins and recovery of autophagosome-lysosome fusion targeted for lysosomes. Meanwhile, Cd-induced lysosomal alkalization due to v-ATPases inhibition was prominently recovered by Qu. Accordingly, Qu enhanced Cd-diminished lysosomal degradation capacity and lysosome-related gene transcription levels. Notably, Qu improved Cd-inhibited TFEB nuclear translocation and its gene transcription level. Furthermore, data showed that the restoration of Cd-impaired autophagy-lysosome pathway and resultant alleviation of cytotoxicity by Qu are TFEB-dependent using TFEB gene silencing and overexpression technologies. In summary, these data provide novel evidences that the protective action of Qu against Cd-induced autophagy inhibition is attributed to its restoration of lysosomal dysfunction, which is dependent on TFEB.


Assuntos
Cádmio/toxicidade , Substâncias Protetoras/farmacologia , Quercetina/farmacologia , Animais , Autofagia/efeitos dos fármacos , Núcleo Celular/metabolismo , Células Epiteliais , Lisossomos/efeitos dos fármacos , Ratos
17.
Ecotoxicol Environ Saf ; 208: 111747, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396073

RESUMO

Residues of the psychoactive drug diazepam (DZP) may pose potential risks to fish in aquatic environments, especially by disrupting their behavioral traits. In this study, female and male zebrafish were subjected to chronic exposure (21 days) to sublethal doses (120 and 12 µg/L) of DZP, aimed to compare the characteristics of their behavioral responses to DZP exposure, and to investigate the possible links between those behavioral responses and variations in their brain γ-aminobutyric acid (GABA) and acetylcholinesterase (AChE) levels. Chronic exposure to DZP significantly decreased the swimming velocity and locomotor activity of both genders, indicating a typical sedative effect. Compared with males, whose locomotor activity was only significantly decreased by exposure to DZP for 21 days, females became hypoactive on day 14 (i.e., more sensitive), and they developed tolerance to the hypoactive effect induced by 120 µg/L DZP by day 21. Exposure to DZP significantly disturbed the behavioral traits related to social interactions in females but not in males. Those results indicate that DZP exhibits sex-dependent effects on the behaviors of fish. Moreover, exposure to DZP for 21 days significantly disturbed almost all of the tested behavioral traits associated with courtship when both genders were put together. Sex-dependent responses in brain GABA and AChE levels due to DZP exposure were also identified. Significant relationships between the brain GABA/AChE levels and some behavioral parameters related to locomotor activity were detected in females, but not in males.


Assuntos
Diazepam/toxicidade , Testes de Toxicidade Crônica , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Acetilcolinesterase/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Diazepam/administração & dosagem , Feminino , Masculino , Atividade Motora/efeitos dos fármacos , Natação , Peixe-Zebra/metabolismo , Ácido gama-Aminobutírico/farmacologia
18.
Ecotoxicol Environ Saf ; 208: 111628, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396148

RESUMO

Metals may cause damage to the biota of contaminated environments. Moreover, using multiple endpoints in ecotoxicological studies is useful to better elucidate the mechanisms of toxicity of these compounds. Therefore, this study aimed to evaluate the effects of cadmium (Cd) and cobalt (Co) on growth, biochemical and photosynthetic parameters of the microalgae Raphidocelis subcapitata, through quantification of lipid classes composition, chlorophyll a (Chl a) content, maximum (ΦM) and effective (Φ'M) quantum yields and efficiency of the oxygen-evolving complex (OEC). Both metals affected the algal population growth, with an IC50-96h of 0.67 and 1.53 µM of Cd and Co, respectively. Moreover, the metals led to an increase in the total lipid content and reduced efficiency of OEC and ΦM. Cell density was the most sensitive endpoint to detect Cd toxicity after 96 h of treatment. Regarding Co, the photosynthetic parameters were the most affected and the total lipid content was the most sensitive endpoint as it was altered by the exposure to this metal in all concentrations. Cd led to increased contents of the lipid class wax esters (0.89 µM) and phospholipids (PL - at 0.89 and 1.11 µM) and decreased values of triglycerides (at 0.22 µM) and acetone-mobile polar lipids (AMPL - at 0.44 and 1.11 µM). The percentage of free fatty acids (FFA) and PL of microalgae exposed to Co increased, whereas AMPL decreased in all concentrations tested. We were able to detect differences between the toxicity mechanisms of each metal, especially how Co interferes in the microalgae at a biochemical level. Furthermore, to the best of our knowledge, this is the first study reporting Co effects in lipid classes of a freshwater Chlorophyceae. The damage caused by Cd and Co may reach higher trophic levels, causing potential damage to the aquatic communities as microalgae are primary producers and the base of the food chain.


Assuntos
Cádmio/toxicidade , Clorofíceas/fisiologia , Cobalto/toxicidade , Poluentes Químicos da Água/toxicidade , Clorofíceas/efeitos dos fármacos , Clorofila A , Ecotoxicologia , Água Doce/química , Metais/farmacologia , Microalgas/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Complexo de Proteína do Fotossistema II
19.
Nat Commun ; 12(1): 61, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397928

RESUMO

Coat protein complex I (COP-I) mediates the retrograde transport from the Golgi apparatus to the endoplasmic reticulum (ER). Mutation of the COPA gene, encoding one of the COP-I subunits (α-COP), causes an immune dysregulatory disease known as COPA syndrome. The molecular mechanism by which the impaired retrograde transport results in autoinflammation remains poorly understood. Here we report that STING, an innate immunity protein, is a cargo of the retrograde membrane transport. In the presence of the disease-causative α-COP variants, STING cannot be retrieved back to the ER from the Golgi. The forced Golgi residency of STING results in the cGAS-independent and palmitoylation-dependent activation of the STING downstream signaling pathway. Surf4, a protein that circulates between the ER/ ER-Golgi intermediate compartment/ Golgi, binds STING and α-COP, and mediates the retrograde transport of STING to the ER. The STING/Surf4/α-COP complex is disrupted in the presence of the disease-causative α-COP variant. We also find that the STING ligand cGAMP impairs the formation of the STING/Surf4/α-COP complex. Our results suggest a homeostatic regulation of STING at the resting state by retrograde membrane traffic and provide insights into the pathogenesis of COPA syndrome.


Assuntos
Retículo Endoplasmático/metabolismo , Homeostase , Proteínas de Membrana/metabolismo , Animais , Brefeldina A/farmacologia , Vesículas Revestidas pelo Complexo de Proteína do Envoltório/efeitos dos fármacos , Vesículas Revestidas pelo Complexo de Proteína do Envoltório/metabolismo , Vesículas Revestidas pelo Complexo de Proteína do Envoltório/ultraestrutura , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/ultraestrutura , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/ultraestrutura , Complexo de Golgi/efeitos dos fármacos , Complexo de Golgi/metabolismo , Complexo de Golgi/ultraestrutura , Células HEK293 , Humanos , Lipoilação , Luciferases/metabolismo , Camundongos , Nucleotidiltransferases/metabolismo , Ligação Proteica/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos
20.
Nat Commun ; 12(1): 62, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397936

RESUMO

Histones control gene expression by regulating chromatin structure and function. The posttranslational modifications (PTMs) on the side chains of histones form the epigenetic landscape, which is tightly controlled by epigenetic modulator enzymes and further recognized by so-called reader domains. Histone microarrays have been widely applied to investigate histone-reader interactions, but not the transient interactions of Zn2+-dependent histone deacetylase (HDAC) eraser enzymes. Here, we synthesize hydroxamic acid-modified histone peptides and use them in femtomolar microarrays for the direct capture and detection of the four class I HDAC isozymes. Follow-up functional assays in solution provide insights into their suitability to discover HDAC substrates and inhibitors with nanomolar potency and activity in cellular assays. We conclude that similar hydroxamic acid-modified histone peptide microarrays and libraries could find broad application to identify class I HDAC isozyme-specific substrates and facilitate the development of isozyme-selective HDAC inhibitors and probes.


Assuntos
Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/metabolismo , Peptídeos/metabolismo , Sequência de Aminoácidos , Células HEK293 , Histonas/metabolismo , Humanos , Isoenzimas/metabolismo , Análise em Microsséries , Peptídeos/química , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Zinco/metabolismo
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